Bioengineering & Translational Medicine最新文献

{"title":"Oral tissue spheroid, organoid, and organ‐on chip microphysiological modeling strategies towards enhanced emulation of health and disease","authors":"Z. Gouveia, A. Özkan, W. V. Giannobile, J. P. Santerre, D. T. Wu","doi":"10.1002/btm2.70020","DOIUrl":"https://doi.org/10.1002/btm2.70020","url":null,"abstract":"Diseases and disorders of dental, oral, and craniofacial (DOC) tissues represent a significant global health burden and have been found to have the greatest age‐standardized prevalence and incidence of all reported diseases worldwide. While the application of novel therapies has been suggested to address the different types of oral health diseases, only a limited number of interventional regenerative therapies have been reported to improve clinical therapeutic outcomes. The lack of novel therapies in DOC tissue regeneration may be in part attributed to the highly resource‐intensive translational path from preclinical models to clinical trials. Recently, stakeholders and regulatory agencies have begun to encourage the use of alternative preclinical models using human tissues for testing therapeutic interventions in place of animal models. This advocacy may provide an opportunity to reduce or eliminate animal testing, ultimately limiting resource expenditure and providing a more efficient regulatory pathway for the approval of novel DOC therapies. While the complexity of DOC physiology, defects, and diseases is not effectively recapitulated in traditional 2D or 3D in vitro culture models, the emergence of more sophisticated in vitro models (or so‐called microphysiological systems that include spheroid, organoid and organ on‐chip (OoC) systems) has enabled effective modeling of clinically simulated disease states in several DOC tissue and organ systems. Here, we aim to provide an overview and collective comparison of these microphysiological systems, outline their current uses in DOC research, and identify important gaps in both their utilization and abilities to recapitulate essential features of native oral‐craniofacial physiology, towards enabling the therapeutic performance of de novo interventions targeted at regeneration outcomes in vivo.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"51 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidic approaches for liquid biopsy in glioblastoma: Insights into diagnostic and follow‐up strategies","authors":"Clara Bayona, Teodora Ranđelović, Claudia Olaizola‐Rodrigo, Ignacio Ochoa","doi":"10.1002/btm2.70032","DOIUrl":"https://doi.org/10.1002/btm2.70032","url":null,"abstract":"Glioblastoma (GBM) is a highly malignant brain tumor with a poor survival prognosis of 12–15 months despite current therapeutic strategies. Diagnosing GBM is challenging, often requiring invasive techniques such as tissue biopsy and imaging methods that can provide inconclusive results. In this regard, liquid biopsy represents a promising alternative, providing tumor‐derived information from less invasive sources such as blood or cerebrospinal fluid. However, the typically low concentrations of these biomarkers pose challenges for traditional detection techniques, limiting their sensitivity and specificity. Recent advances in microfluidics offer a potential solution by enhancing the isolation and detection of tumor‐derived cells and molecules, thus improving their detectability. This review discusses the latest progress in microfluidic‐based liquid biopsy systems for glioblastoma, laying the basis for future diagnostic practices that are less invasive and more accurate. As these technologies evolve, they hold the potential to transform GBM diagnosis and monitoring, ultimately improving patient outcomes.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"76 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial and photosynthetic therapy: A crucial strategy for remodeling cellular metabolic function","authors":"Muhammad Samee Mubarik, Zizhen Zhao, Mehdi Khoshnamvand, De‐Sheng Pei, Ailing Fu","doi":"10.1002/btm2.70027","DOIUrl":"https://doi.org/10.1002/btm2.70027","url":null,"abstract":"Extranuclear organelle transplantation, an emerging field in cell biology and bioengineering, presents innovative therapeutic possibilities by transferring organelles such as mitochondria between cells or across species. In living organisms, mitochondria and chloroplasts are closely related to converting substances and energy within cells. Transplantation therapy of mitochondria seeks to rebuild cell metabolic function in diseased or damaged cells and has broad application potential in treating metabolic diseases. The therapies provide a distinctive technology for cellular restoration by targeting energy generation at the organelle level, which will offer new energy resources for animal cells. At present, mitochondrial transplantation therapy has been applied as a novel approach to rescue patients in clinical settings, and chloroplast‐based transplantation endows animal cells to utilize light energy (photosynthetic animal cells). In this review, we discuss the exciting development and application prospects of mitochondrial and photosynthetic therapy in biomedicine. The technology of extranuclear transplantation would exert innovative and profound impacts on biological therapy.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"25 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic and proteomic signatures differentiate inflammatory phenotypes from cancer and predict treatment response in patient sera","authors":"Gabriel Cutshaw, Elena V. Demidova, Philip Czyzewicz, Elizabeth Quam, Nicole Lorang, AL Warith AL Siyabi, Surinder Batra, Sanjeevani Arora, Rizia Bardhan","doi":"10.1002/btm2.70029","DOIUrl":"https://doi.org/10.1002/btm2.70029","url":null,"abstract":"Tumors shift their metabolic needs to enable uncontrolled proliferation. Therefore, metabolic assessment of cancer patient sera provides a significant opportunity to noninvasively monitor disease progression and enable mechanistic understanding of the pathways that lead to response. Here, we show Raman spectroscopy (RS), a highly sensitive and label‐free analytical tool, is effective in metabolic profiling across diverse cancer types in patient sera from both pancreatic ductal adenocarcinoma (PDAC) and locally advanced rectal cancer (LARC). We also combine metabolic data with proteomic signatures to predict treatment response. Our data show RS peaks successfully differentiate PDAC patients from healthy controls. Peaks associated with sugars, tyrosine, and DNA/RNA distinguish PDAC patients from chronic pancreatitis, an inflammatory condition that is notoriously difficult to discern from PDAC via current clinical approaches. Furthermore, our study is expanded to investigate response to chemoradiation therapy in LARC patient sera where at pre‐treatment multiple metabolites including glycine, carotenoids, and sugars are jointly correlated to the neoadjuvant rectal (NAR) score indicative of poor prognosis. Via classical univariate AUC–ROC analysis, several RS peaks were found to have an AUC>0.7, highlighting the potential of RS in identifying key metabolites for differentiating complete and poor responders of treatment. Gene set enrichment analysis revealed enrichment of metabolic, immune, and DDR‐related pathways associated with CRT response. Notably, RS‐derived metabolites were significantly correlated with multiple immune signaling proteins and DDR markers, suggesting these distinct analytes converge to reflect systemic changes within the tumor microenvironment. By integrating metabolic, proteomic, and DDR data, we identified pre‐treatment activation of galactose and glycerolipid metabolism, and post‐treatment engagement of cell cycle and p53 signaling pathways. Our findings show that RS, when integrated with complementary protein marker analysis, holds the potential to bridge the translational divide enabling a clinically relevant approach for both diagnosis and predicting response in patient samples.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"30 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergizing photodynamic therapy and ethanol ablation: Light‐activatable sustained‐exposure ethanol injection technology for enhanced tumor ablation","authors":"Chen‐Hua Ma, Jeffrey Yang, John A. Quinlan, Kathryn McNaughton, Michele L. Kaluzienski, Tessa Hauser, Matthew F. Starost, Jenna L. Mueller, Huang‐Chiao Huang","doi":"10.1002/btm2.70028","DOIUrl":"https://doi.org/10.1002/btm2.70028","url":null,"abstract":"Chemical ablative therapies offer effective alternatives for tumor treatment, particularly when surgical resection or heat‐based ablation therapies are unsuitable due to the tumor's stage, location, or extent. Photodynamic therapy (PDT), which involves delivering light‐activated, tumor‐killing photosensitizers, and percutaneous ethanol injection (PEI), which involves the direct injection of pure ethanol into tumor nodules, are two non‐heat‐based chemical ablative methods that have been proven safe with low adverse effects for unresectable tumors. We have investigated combining these two treatments using a new formulation known as BPD‐EC‐EtOH. This formulation includes three components: (1) benzoporphyrin derivative, a commonly used photosensitizer for PDT; (2) ethyl cellulose (EC), an FDA‐approved polymer that forms a gel in the water phase and enhances drug retention; and (3) pure ethanol for PEI application. Here, we demonstrated the localization of BPD and confirmed that it retains its photochemical properties within the EC‐EtOH gel in tissue‐mimicking phantoms and in swine liver tissues. We also characterized EC's ability to act as a light‐scattering agent, which effectively extends light propagation distance in both in vitro models and ex vivo porcine liver tissues, potentially overcoming the limitations of light penetration in pigmented organs. We then investigated the therapeutic effects of BPD‐EC‐EtOH using two well‐established subcutaneous animal models of hepatocellular carcinoma and pancreatic ductal adenocarcinoma, both in single‐ and multi‐cycle combination treatments, showing tumor‐killing effects. These findings highlight the potential of BPD‐EC‐EtOH as a novel therapeutic approach, effective with either single or multi‐cycle treatment sessions.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"130 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self‐assembly of verteporfin dimers into folate receptor‐targeted lipid nanoparticles for photodynamic therapy of ovarian cancer","authors":"Carla Arnau del Valle, Payal Srivastava, Kathryn McNaughton, Huang‐Chiao Huang","doi":"10.1002/btm2.70031","DOIUrl":"https://doi.org/10.1002/btm2.70031","url":null,"abstract":"Photodynamic therapy (PDT) is a minimally invasive treatment that involves the administration of a light‐activatable drug followed by light activation of the lesion to produce reactive oxygen species that kill cancer cells. Visudyne®, a liposomal formulation of benzoporphyrin derivative (BPD) photosensitizer, is clinically approved for PDT of ocular diseases and is now being tested for PDT and imaging of pancreatic, brain, and other cancers. While Visudyne® improves the pharmacokinetics of BPD, it lacks treatment selectivity. To reduce PDT‐associated side effects such as skin and bowel toxicity while enhancing therapeutic outcomes, developing cancer‐targeted BPD nanotechnology is essential. Many cancers are characterized by overexpression of folate receptor (FR) and present high levels of glutathione (GSH). Here, we report the synthesis of a dimeric‐BPD (dBPD) activatable by red light for PDT and imaging of cancer cells. Self‐assembled lipid nanoparticles (NPs) are developed by the aggregation of dBPD and further functionalized with FA (FA‐dBPD‐NPs) and with drug release capability via cleavage of the disulfide linkers through GSH. The FA‐dBPD‐NPs present high drug payload, GSH‐triggered release effect, FRs overexpressing cell targeting, endoplasmic reticulum accumulation, and effective PDT in ovarian cancer cells.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"14 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing a novel adult erythroid cell line for red blood cell manufacture","authors":"David Phillips, Marianne J. Ellis, Jan Frayne, Sandhya Moise","doi":"10.1002/btm2.70026","DOIUrl":"https://doi.org/10.1002/btm2.70026","url":null,"abstract":"One way to address the growing shortage of donated blood required for routine and emergency transfusion is to mass‐manufacture red blood cells (RBCs) in vitro. However, numerous biological and bioprocessing challenges must be overcome to realize this goal. In addressing these challenges, a promising solution is the erythroid progenitor cell line, BEL‐A (Bristol Erythroid Line—Adult). Despite this, BEL‐A cells are a recent creation and are currently poorly characterized, which is essential to identify the bioprocess necessary for their mass manufacture. To address this knowledge gap, we provide the first work to characterize BEL‐A cell growth, metabolic kinetics, and tolerance to inhibitory metabolites. Our detailed characterization shows that under static batch culture, BEL‐A cell numbers decline beyond 70 h, which cannot be explained by exhaustion of glucose, glutamine, or doxycycline; excess lactate or ammonia; or by pH. BEL‐A cell viability was shown to be more sensitive to ammonia than lactate, while combinatorial concentrations of 2640 mg/L lactate and 129 mg/L ammonia mediated cell death. Finally, daily media replenishment was able to overcome the 70 h proliferation limit, enabling higher density cultures. As a result, we report for the first time the key cellular characteristics crucial for facilitating high‐density BEL‐A cell manufacture within bioreactors, at scale and identify optimal conditions for their in vitro culture. This study therefore represents a critical step in realizing BEL‐A cells' clinical potential as a cell source for large‐scale manufacture of RBCs.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early nanoparticle intervention preserves motor function following cervical spinal cord injury","authors":"Sarah E. Hocevar, Brian C. Ross, Yinghao Wang, Cecelia R. Crowther, Samantha R. Schwartz, Brain J. Cummings, Aileen J. Anderson, Lonnie D. Shea","doi":"10.1002/btm2.70011","DOIUrl":"https://doi.org/10.1002/btm2.70011","url":null,"abstract":"Spinal cord injury (SCI) triggers an immediate influx of immune cells that secrete pro‐inflammatory cytokines and reactive oxygen species that cause tissue damage that is secondary to the initial physical trauma. We aim to reprogram these immune cells to promote a less inflammatory and more pro‐regenerative environment. Herein, we investigated the window in time during which poly(lactide‐co‐glycolide) nanoparticles (NPs) administration can successfully modulate the immune response and promote functional sparing. The dynamics of immune cell infiltration and secondary tissue damage were studied following the injection of NPs intravenously every 24 h for 7 days following injury, with the first injection starting at 2, 4, or 24 hours post‐injury (hpi). At 7 days post‐injury (dpi), early NP intervention decreased the number of infiltrating macrophages and neutrophils, but delaying treatment until 24 hpi increased the number of neutrophils above control. All mice that received NPs had greater neuronal sparing contralateral to the injury, but mice that received NPs at early timepoints had greater neuromuscular junction innervation and motor endplate sparing. The increased sparing of neurons and neural circuits in the 2 hpi NP group corresponded with increased motor function, as measured by a ladder beam test. Collectively, these results suggest that early intervention with NPs can modulate the inflammatory response and preserve motor function and circuits following SCI.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"19 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitomycin C‐immobilized silver nanoparticle‐loaded polycaprolactone membrane for temporary scalp expansion after decompressive craniectomy to prevent wound infection","authors":"Kai‐Lun Liu, Ya‐Jyun Liang, Kuo‐Hsiang Hung, Yu‐Ning Chen, Feng‐Huei Lin","doi":"10.1002/btm2.70023","DOIUrl":"https://doi.org/10.1002/btm2.70023","url":null,"abstract":"Malignant cerebral edema (MCE) represents a significant medical emergency characterized by unmanageable intracranial pressure (ICP), frequently arising as a consequence of traumatic brain injury (TBI) or ischemic stroke. Decompressive craniectomy (DC) is a prevalent surgical procedure employed to mitigate elevated ICP by excising a segment of the skull to enhance intracranial volume. Nevertheless, in patients suffering from MCE, the limited capacity for expansion of the scalp subsequent to DC may lead to sustained elevated ICP and complications including wound‐edge necrosis, cerebrospinal fluid leakage, and infection. This investigation seeks to formulate a biocompatible, antibacterial, and anti‐adhesive membrane intended for temporary scalp expansion following DC, thereby addressing these pressing concerns. The proposed membrane comprises polycaprolactone (PCL) augmented with silver nanoparticles (AgNPs) to confer antibacterial properties and is further immobilized with Mitomycin C (MMC) to minimize tissue adhesion, thereby facilitating more straightforward removal. The selection of PCL was predicated upon its remarkable mechanical strength and ductility, which make it suitable for withstanding intracranial edema and facilitating the suturing protocol. The AgNPs were synthesized through a green synthesis methodology employing epigallocatechin gallate (EGCG) to ensure environmental sustainability and the stability of the resultant nanoparticles. MMC, known for its anti‐proliferative attributes, was affixed to the PCL surface via oxygen plasma treatment, thereby enhancing the anti‐adhesive properties of the membrane. This study evaluates the mechanical characteristics, antibacterial effectiveness, anti‐adhesive capabilities, and biocompatibility of the PCL/AgNPs/MMC membrane, thereby demonstrating its potential to improve outcomes in DC procedures by increasing intracranial volume and reducing postoperative complications.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"87 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo immunogenicity assessment of a multiepitope‐displayed phage vaccine against Brucella species infection in BALB/c mice","authors":"Mahmood Fadaie, Mahsa Esmaeilifallah, Anis Khalafiyan, Ilnaz Rahimmanesh, Seyed Hossein Hejazi, Hossein Khanahmad","doi":"10.1002/btm2.70024","DOIUrl":"https://doi.org/10.1002/btm2.70024","url":null,"abstract":"Bacteriophages are considered ideal vaccine platforms owing to their safety, intrinsic adjuvant properties, stability, and low‐cost production. One of the best strategies to prevent brucellosis in humans and animals is vaccination. For several years, researchers have dedicated their efforts to enhance the effectiveness and safety of the Brucella vaccine. This study was designed to evaluate the immunogenicity of a phage vaccine displaying multiepitopes from six different Brucella protective proteins in a mouse model. This study used immunoinformatics to predict T‐ and B‐cell epitopes. Subsequently, a multiepitope protein was synthesized and recombinant phages displaying the multiepitope protein were prepared. The multiepitope protein display on the phage was confirmed by Western blot analysis. Six groups of BALB/c mice (6 mice per group) received multiepitope phage (as a vaccine), helper phage, and PBS as controls subcutaneously or orally. An ELISA assay was used to analyze the humoral response in mouse serum, while an interferon‐gamma ELISpot assay was performed on mouse splenocytes to evaluate the cell‐mediated immune response. Mice immunized with multiepitope phage showed significant serum levels of specific IgG and significant numbers of specific IFN‐producing T cells in splenic lymphocytes (<jats:italic>p</jats:italic>‐value &lt;0.05). The oral administration route provided a much stronger cellular response than a subcutaneous injection (about 10‐fold), which is important for combating brucellosis infection. These findings provide the first evidence that a multiepitope‐displayed phage vaccine may be a promising avenue for developing a safe and efficient vaccine against Brucella species.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"31 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}